A 2A receptor antagonism and dyskinesia in parkinson's disease

Micaela Morelli, Fabio Blandini, Nicola Simola, Robert A. Hauser

Research output: Contribution to journalArticlepeer-review

Abstract

Dyskinesia, a major complication of treatment of Parkinson's disease (PD), involves two phases: induction, which is responsible for dyskinesia onset, and expression, which underlies its clinical manifestation. The unique cellular and regional distribution of adenosine A 2A receptors in basal ganglia areas that are richly innervated by dopamine, and their antagonistic role towards dopamine receptor stimulation, have positioned A 2A receptor antagonists as an attractive nondopaminergic target to improve the motor deficits that characterize PD. In this paper, we describe the biochemical characteristics of A 2A receptors and the effects of adenosine A 2A antagonists in rodent and primate models of PD on L-DOPA-induced dyskinesia, together with relevant biomarker studies. We also review clinical trials of A 2A antagonists as adjuncts to L-DOPA in PD patients with motor fluctuations. These studies have generally demonstrated that the addition of an A 2A antagonist to a stable L-DOPA regimen reduces OFF time and mildly increases dyskinesia. However, limited clinical data suggest that the addition of an A 2A antagonist along with a reduction of L-DOPA might maintain anti-Parkinsonian benefit and reduce dyskinesia. Whether A 2A antagonists might reduce the development of dyskinesia has not yet been tested clinically.

Original languageEnglish
Article number489853
JournalParkinson's Disease
DOIs
Publication statusPublished - 2012

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Clinical Neurology
  • Psychiatry and Mental health

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